A clinical trial study to assess the effects of Bempedoic acid on heart related events in patients with or at high risk for heart related issues who are unable to tolerate statins (class of drugs that reduce cholesterol in blood)
Scientific Title of Study
A Randomized, Double-Blind, Placebo Controlled Study To Assess The Effects Of Bempedoic Acid (Etc-1002) On The Occurrence Of Major Cardiovascular Events In Patients With, Or At High Risk For, Cardiovascular Disease Who Are Statin Intolerant
IQVIA RDS (India) Private Ltd
Natraj by Rustomjee 6th Floor, 194 MV Road, Near Western Express Highway Metro Station
Andheri East, Mumbai 400 069,
Maharashtra, India
IQVIA RDS (India) Private Ltd
Natraj by Rustomjee 6th Floor, 194 MV Road, Near Western Express Highway Metro Station
Andheri East, Mumbai 400 069,
Maharashtra, India
Mumbai MAHARASHTRA 400069 India
Phone
912266774242
Fax
912266774343
Email
suneela.thatte@quintiles.com
Source of Monetary or Material Support
Esperion Therapeutics, Inc.
3891 Ranchero Drive, Suite 150
Ann Arbor, MI 48108
United States of America
Primary Sponsor
Name
Esperion Therapeutics Inc
Address
Esperion Therapeutics, Inc.
3891 Ranchero Drive, Suite 150
Ann Arbor, MI 48108
United States of America
Type of Sponsor
Pharmaceutical industry-Global
Details of Secondary Sponsor
Name
Address
Quintiles Research India Private Limited
B 101-106, Shapath IV, Opp Karnavati Club- Sarkhej Ghandi Nagar Road Ahmedabad 380051, India
Countries of Recruitment
Argentina Australia Brazil Bulgaria Chile Colombia Croatia Czech Republic Denmark Estonia Germany Hungary India Latvia Lithuania Mexico Netherlands Poland Romania Russian Federation Serbia Slovakia South Africa Spain Turkey Ukraine United Kingdom United States of America
Department of Research 14 Floor C Wing Super Speciality building Deenanath Mangeshkar Hospital and Research Centre off Karve Road Erandawane Pune-411004, Maharashtra. India
Eternal Heart Care Centre & Research Institute - Institutional Ethics Committee 3 A, Jagatpura Road, Near Jawahar Circle, Jaipur - 302020, Rajasthan, India
Approved
Ethics Committee Kamalnayan Bajaj Hospital, Marathawada Medical & Research Institute, Gut No.43, Satara Parisar, Bajaj Marg, Beed Bypass Road, Aurangabad-431005, Maharashtra, India
Approved
Ethics Committee, Fortis Escorts Hospital, Neelam Bata Road, Faridabad-121001, Haryana, India
Ethics Committee,MAMC Loknayak Hospital, Room No 122 B.L.Taneja block MAMC,LNJP Hospital, New Delhi-110002, India
Approved
Institutional Ethics Committee of B. J. Government Medical College & Sassoon General Hospitals, Pune-411001, Maharashtra, India
Approved
Institutional Ethics Committee of Kovai Diabetes Speciality Centre & Hospital,No.15, Vivekananda Road, Ramnagar, Coimbatore-641009Tamilnadu, India
Approved
institutional Ethics Committee, Government Medical College and Hospital, Department of Medicine, Medical College Square Road, Nagpur-440003, Maharashtra, India.
Approved
Institutional Ethics Committee, Government Medical College, Aurangabad-431001, Maharashtra, India
Approved
Institutional Ethics Committee, The Madras Medical Mission, 4-a, Dr.J.J.Nagar, Mogappair, Chennai - 600037, Tamilnadu, India
Approved
KRM Hospital Ethics Commitee,KRM Hospital and Research Centre, 3/92-93, Vijayant Khand, Gomtinagar, Lucknow-226010, Uttar Pradesh
Approved
Meditrina Institute Ethics Committee 278, Central Bazar Road, Ramdaspeth, Nagpur-440010, Maharashtra, India
Approved
O & P Institutional Ethics Committe, 2 Floor,1671-75,Ganeshkhind Road, Shivajinagar,Pune-411005
Approved
Rhythm Heart Institute Ethics Committee, Near Siddharth Bunglows,, Sama- Savli Road, Vadodara-390022, Gujarat, India
Approved
S.R.Kalla Memorial Ethical Committee for Human Research, S R Kalla Memorial Gastro & General Hospital 78-79, Dhuleshwar Garden, Behind HSBC Bank, Sardar Patel Marg, C-Scheme, Jaipur-302001 Rajasthan, India.
Approved
Scientific Research And Ethical Review CommiteeDepa1tment of Laboratory Medicine, Batra Hospital & Medical Research Centre, I, TughlakabadInstitutional Area, Mehrauli-Badarpur Road, New Delhi-110062
Approved
Shri B.D. Mehta Mahavir Heart Institute Ethics Committee
Approved
Sushruta Hospitals Ethics Committee C/ O Sushruta Multispeciality Hospital & Research Centre Private Limited., P. B. Road, Vidyanagar, Hubli-580021, Dharwar, Karnataka, India.
1.Provision of signed informed consent prior to any study-specific procedure.
2. Patient reported statin intolerance (SI) due to an adverse safety effect that started or increased during statin therapy and resolved or improved when statin therapy was discontinued resulting in an inability to tolerate:
• 2 or more statins at any dose, or
• 1 statin at any dose and unwilling to attempt a second statin or advised by a physician to not attempt a second statin.
3. Written confirmation by both patient and investigator that the patient is statin intolerant as defined above, aware of the benefit of statin use to reduce the risk of MACE including death, and also aware that many other patients who are unable to tolerate a statin are able to tolerate a different statin or dose.
4. Age ≥18 years or legal age of majority based on regional law, whichever is greater, and ≤85 years at Week -5 (Visit S1).
5.Men and nonpregnant, nonlactating women. Women must be one of the following:
a.Naturally postmenopausal defined as ≥1 year without menses and:
•≥55 years, or
•<55 years with follicle-stimulating hormone (FSH) ≥40.0 IU/L, or
b.Surgically sterile including hysterectomy, bilateral oophorectomy, and/or tubal ligation,
or
c.Women of childbearing potential willing to use one acceptable method of birth control during the study and for 30 days after the end of treatment including:
•oral birth control medications,
•placement of an intrauterine device with or without hormones,
•barrier methods including condom or occlusive cap with spermicidal foam or spermicidal jelly,
•vasectomized male partner who is the sole partner for this patient,
•true abstinence (not including periodic abstinence such as calendar, ovulation, symptothermal, postovulation methods, or withdrawal).
There are no protocol-specific birth control requirements for men with partners who are able to become pregnant.
6. Fasting LDL-C ≥100 mg/dL (2.6 mmol/L) at Week -5 (Visit S1) while taking stable (4 weeks prior to Visit S1) and optimized background LDL-C-lowering therapies that may include very low dose statin (see definition above), ezetimibe, niacin, bile acid resins, fibrates, and/or proprotein convertase subtilisin kexin type 9 (PCSK9) inhibitors.
Note: A single repeat of LDL-C may be completed prior to initiation of the single-blind Run–in Period. For those patients who have a repeat LDL-C, the repeat value will be used to determine eligibility.
7.History of, or at high risk for, CVD including documented evidence of one or more of the following:
a.Coronary artery disease, defined by:
•MI (either ST-elevation MI or non-ST-elevation MI) occurring greater than 90 days prior to screening, or
•Percutaneous coronary or surgical coronary revascularization, occurring greater than 90 days prior to screening, or
•Angiographic stenosis of >50% in a least 1 major coronary artery (native or graft vessel), as documented by selective coronary angiography or computed tomography angiography (CTA), or
b.Symptomatic peripheral arterial disease (PAD) , defined by:
•Peripheral vascular disease with symptoms of claudication or resting limb ischemia with either ankle brachial index <0.9 performed by a vascular lab or angiogram (including CTA) showing ≥50% stenosis, or
•Peripheral arterial revascularization (surgical or percutaneous), occurring greater than 90 days prior to screening, or
•Abdominal aortic aneurysm confirmed by imaging or aortic aneurysm repair, occurring greater than 90 days prior to screening, or
•Lower extremity amputation due to peripheral vascular disease, occurring greater than 90 days prior to screening, or
c.Cerebrovascular atherosclerotic disease defined by:
•Ischemic stroke occurring greater than 90 days prior to screening, or
•Carotid endarterectomy, carotid stenting, or more than 70% stenosis in a carotid artery determined by carotid ultrasound or angiogram, occurring greater than 90 days prior to screening, or
d.High risk for a CVD event, defined by:
•Reynolds Risk score >30% or a SCORE Risk score >7.5% over 10 years, or
•Coronary artery calcium score >400 Agatston units (AU) at any time in the past.
ExclusionCriteria
Details
Patients who meet any of the following criteria will not be eligible to participate:
1.Total fasting TG >500 mg/dL (5.6 mmol/L) at Week -5 (Visit S1).
Note: A single repeat of TG may be completed prior to initiation of the single-blind Run-in Period. For those patients who have a repeat TG, the repeat value will be used to determine eligibility.
2.Renal dysfunction or a glomerulonephropathy defined as either nephritic or nephrotic syndrome, including estimated glomerular filtration rate (eGFR; using central laboratory determined Modification of Diet in Renal Disease [MDRD] formula) <30 mL/min/1.73 m2 at Week -5 (Visit S1).
Note: A single repeat of eGFR may be completed prior to randomization. For those patients who have a repeat eGFR, the repeat value will be used to determine eligibility.
3.Forms of CVD that include any of the following:
a.Recent (within 90 days prior to screening) transient ischemic attack (TIA)
b.Recent (within 90 days of screening) unstable or symptomatic cardiac arrhythmia (including any associated medication changes). Patients with stable well-controlled atrial arrhythmias will be allowed to participate in the study.
c.Patients with implantable pacemakers or automatic implantable cardioverter defibrillators may be considered if deemed by the investigator to be stable for greater than 90 days prior to screening,
d.New York Heart Association (NYHA) Functional Classification Class IV heart failure,
e.Uncontrolled hypertension, defined as mean sitting systolic blood pressure (SBP)
≥180 mmHg and/or diastolic blood pressure (DBP) ≥110 mmHg,
f.Planned coronary revascularization (patient may rescreen 3 months post-procedure).
Note: At the discretion of the investigator, BP medications can be adjusted and/or additional assessment of BP may be completed prior to randomization, with the repeat assessment value used to determine eligibility. Alternatively, patients can be rescreened if BP status has changed.
4.HbA1C ≥10% at Week -5 (Visit S1).
5.Uncontrolled hypothyroidism, including thyroid-stimulating hormone (TSH) >1.5 × the upper limit of normal (ULN) at Week -5 (Visit S1). Note: At the discretion of the investigator, thyroid replacement therapy can be adjusted and/or additional measurement of TSH may be completed prior to randomization, with the repeat TSH value used to determine eligibility.
6.Liver disease or dysfunction, including:
a. Positive serology for hepatitis B surface antigen (HBsAg) and/or hepatitis C antibodies (HCV-ABVivi) at Week -4 (Visit S2), or
b. Alanine aminotransferase (ALT) and/or aspartate aminotransferase (AST) ≥2.0 × ULN at Week -5 (Visit S1).
Note: At the discretion of the investigator, a single repeat of ALT and/or AST may be completed prior to randomization. For those patients who have a repeat ALT and/or AST, the repeat value will be used to determine eligibility. Also, if test for Hepatitis C antibody is positive, but optional reflexive test for Hepatitis C RNA is negative, patient can be enrolled.
7.Gastrointestinal conditions or procedures (including weight loss surgery; eg, Lap-Band® or gastric bypass) that may affect drug absorption.
8.Hematologic or coagulation disorders or a hemoglobin (Hgb) level <10 g/dL at Week -5 (Visit S1).
9.Active malignancy, including those requiring surgery, chemotherapy, and/or radiation in the past 5 years. Nonmetastatic basal or squamous cell carcinoma of the skin and cervical carcinoma in situ are allowed.
10.Unexplained creatine kinase (CK) >3 × ULN at Week -5 (Visit S1) (ie, not associated with recent trauma or physically strenuous activity). Patients with an explained CK elevation must have single repeat CK ≤3 × ULN prior to randomization.
11.History within the last 2 years of drug, alcohol, amphetamine and derivatives, or cocaine abuse. Patients with amphetamine derivatives prescribed by and under the care of a health care practitioner can be enrolled after evaluation by the investigator.
12.Blood transfusion for any reason within 30 days prior to randomization.
13.Use of any experimental or investigational drugs within 30 days prior to screening or 5 half-lives, whichever is longer.
14.Randomization into another Phase 3 bempedoic acid clinical study.
15.Use of, or a plan to initiate, these prohibited therapies/supplements during the study:
a. Mipomersen (must be stopped at least 6 months prior to Week -5 [Visit S1]), lomitapide or apheresis therapy (must be stopped at least 3 months prior to Week -5 [Visit S1]),
b.Red yeast rice (must be stopped at least 2 weeks prior to Week -5 [Visit S1]),
c.Statins are prohibited at average daily doses of rosuvastatin ≥5 mg, atorvastatin ≥10 mg, simvastatin ≥10 mg, lovastatin ≥20 mg, pravastatin ≥40 mg, fluvastatin ≥40 mg, or pitavastatin ≥2 mg.
16.Planned initiation or dose adjustments of these allowed drugs less than 4 weeks prior to screening and during the clinical trial (stable use of these drugs is permitted):
a. Statins are allowed only at average daily doses of rosuvastatin <5 mg, atorvastatin
<10 mg, simvastatin <10 mg, lovastatin <20 mg, pravastatin <40 mg, fluvastatin <40 mg, or pitavastatin <2 mg,
b.Other lipid regulating drugs or supplements.
17.Lack of adherence (ie, less than 80% of planned doses) with IMP (single-blind placebo) during the Run-in Period.
18.Lack of tolerance with IMP (single-blind
19.A medical or situational (ie, geographical) finding that in the investigator’s opinion may compromise the patient’s safety or ability to complete the study.
20. An employee or contractor of the facility conducting the study, or a family member of the Principal Investigator, Co-Investigator, or Sponsor.
Method of Generating Random Sequence
Computer generated randomization
Method of Concealment
Centralized
Blinding/Masking
Participant, Investigator, Outcome Assessor and Date-entry Operator Blinded
To evaluate whether long-term treatment with bempedoic acid 180 mg/day versus placebo reduces the risk of major adverse cardiovascular events (MACE) in patients with, or at high risk for, cardiovascular disease (CVD) who are statin intolerant. This will be assessed with a composite primary efficacy endpoint that includes time to first occurrence of cardiovascular (CV) death, nonfatal myocardial infarction (MI), nonfatal stroke, or coronary revascularization
To evaluate whether long-term treatment with bempedoic acid 180 mg/day versus placebo reduces the risk of other clinical endpoints of CV morbidity & mortality & all-cause mortality
During entire study
To evaluate the effect of long-term treatment with bempedoic acid 180 mg/day versus placebo on low-density lipoprotein cholesterol (LDL-C) and high-sensitivity C-reactive protein (hsCRP)
During entire study
To evaluate the long-term safety and tolerability of bempedoic acid 180 mg/day compared to placebo
During entire study
To evaluate the 12-month efficacy of treatment with bempedoic acid 180 mg/day versus placebo on absolute change in hemoglobin A1c (HbA1C) in the inadequately controlled diabetes efficacy population (patients with diabetes & having an HbA1C of 7% or greater at baseline)
During entire study
To evaluate whether long-term treatment with bempedoic acid 180 mg/day versus placebo reduces the risk of new-onset diabetes in the prediabetes efficacy population (patients with prediabetes at baseline)
During entire study
Target Sample Size
Total Sample Size="12604" Sample Size from India="661" Final Enrollment numbers achieved (Total)= "Applicable only for Completed/Terminated trials" Final Enrollment numbers achieved (India)="Applicable only for Completed/Terminated trials"